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Purpose: The advantages of biological meshes for ventral hernia repair are still under debate. Given the high financial cost, the proper indications for biological meshes should be clarified to restrict their use to properly selected patients., Methods: A retrospective database was instituted to register all cases of abdominal wall defect treated with biological meshes from 1/2010 to 3/2016., Results: A total of 227 patients (mean age: 64 years) whose ventral abdominal defects were reconstructed with a biological mesh were included in the study. Patients were divided according to the 2010 four-level surgical-site complication risk grading system proposed by the Ventral Hernia Working Group (VHWG): Grade 1 (G1, 12 cases), Grade 2 (G2, 68 cases), Grade 3 (G3, 112 cases), and Grade 4 (G4, 35 cases). The surgical site complication rate was higher in patients with one or more risk factors (33.6% vs 19% in patients with no risk factors) (P = 0.68). Statistically significant risk factors associated with the onset of one or more postoperative surgical site complications included: diabetes, coronary artery disease, immunosuppression, and obesity. Recurrence was more common in patients with surgical site complications and mainly associated with infection (38.9%) and wound necrosis (44.4%), and in cases of inlay positioning of the mesh (36%)., Conclusions: Due to their high costs, biological mesh should not be used in G1 patients. In infected fields (G4), they should only be used if no other surgical solution is feasible. There is a clear need to prospectively evaluate the performance of biological meshes.